A model of the acquired immunodeficiency syndrome (AIDS) has been created through the introduction of the human immunodeficiency virus 1 (HIV-1) proviral DNA into the mouse germ line. One of the HIV transgenic founder animals have produced offspring which manifest several symptoms consistent with human AIDS. These are: retardation of growth, skin lesions resembling pronounced spidermal proliferation, pulmonary perivascular lymphocytic infiltrates, and lymphadenopathy. All the affected animals die by day 30 of life. The infectious HIV has been recovered from some tissues of the diseased animals. These results show that the HIV transgenic mouse system can be used as a valuable tool in eliciting the pathogenesis of AIDS, and testing potential treatments for this disease. To study the effects of autoimmune response to a pre-determined immunogen, we have created mice carrying the structural gene of the herpes virus 1 glycoprotein D (gD). The introduced gD construct contains, as a regulatory element, the insulin promoter (pIPEgD), or SV40 promoter (pSVgD). We have expected that the expression of gD in the pancreatic beta cells (pIPEgD transgenics), or in a broad range of other tissues (pSVgD transgenics) will induce the immune responses, at least in some cases. At this stage, animals from only one pSVgD transgenic line have been shown to mount spontaneous anti-gD antibodies. No apparent abnormalities have been observed in these animals. Two other pSVgD lines appear to be tolerant to gD. We intend to identify the tissue localization of gD expression, and look for the effects of augmenting the immune response with recombinant vaccinia-gD, or of breaking the state of tolerance.